Increasing the representation of minoritized youth for inclusive and reproducible brain-behavior associations

Population neuroscience datasets allow researchers to estimate reliable effect sizes for brain-behavior associations because of their large sample sizes. However, these datasets undergo strict quality control to mitigate sources of noise, such as head motion. This practice often excludes a disproportionate number of minoritized individuals. We employ motion-ordering and motion-ordering+resampling (bagging) to test if these methods preserve functional MRI (fMRI) data in the Adolescent Brain Cognitive Development Study (N=5,733). Black and Hispanic youth exhibited excess head motion relative to data collected from White youth, and were discarded disproportionately when using conventional approaches. Both methods retained more than 99% of Black and Hispanic youth. They produced reproducible brain-behavior associations across low-/high-motion racial/ethnic groups based on motion-limited fMRI data. The motion-ordering and bagging methods are two feasible approaches that can enhance sample representation for testing brain-behavior associations and fulfill the promise of consortia datasets to produce generalizable effect sizes across diverse populations.

Supplementary Figure 3. Bootstrap brain-behavior correlations obtained from the standard and bagged methods at typical sample size (N = 25) with (A-B) and without (C-D) excluding the high-motion youth across the 3 racial/ethnic groups.The teal and purple data points corresponded to bootstrap samples at N = 25 obtained from 500 iterations and these samples were used to compute the associations between functional connectivity and NIH Toolbox and CBCL-externalizing.The Lin's concordance correlation coefficient ( c ) and ρ Pearson correlation coefficient (r) were computed respectively to assess the reproducibility and similarity of the brain-behavior associations obtained from the standard and bagging methods.The low-/high-motion youth were retained based on the assumption that they had a minimum of 100 least motion-corrupted timepoints in their fMRI timeseries.
Supplementary Figure 4. Bootstrap brain-behavior correlations obtained from the standard and bagging methods at large sample size (N = 250) with (A-B) and without (C-D) excluding the high-motion youth across the 3 racial/ethnic groups.The teal and purple data points corresponded to bootstrap samples at N = 250 obtained from 500 iterations and these samples were used to compute the associations between functional connectivity and NIH Toolbox and CBCL-externalizing.The Lin's concordance correlation coefficient ( c ) and ρ Pearson correlation coefficient (r) were computed respectively to assess the reproducibility and similarity of the brain-behavior associations obtained from the standard and bagging methods.The low-/high-motion youth were retained based on the assumption that they had a minimum of 100 least motion-corrupted timepoints in their fMRI timeseries.The effect sizes produced by the standard and motion-ordered methods from REST1 were comparable for the NIH Toolbox (0.20% < AUC < 5.03%) and CBCL-externalizing (1.31% < AUC < ∆ ∆ 4.06%) across the 3 low-motion racial/ethnic groups.

Supplementary Figure 6. Correlations between functional connectivity and (A-B) NIH Toolbox and (C-D)
CBCL-externalizing using the standard and motion-ordered methods as a function of sample size across the 3 low-motion racial/ethnic groups obtained from REST1.The respective edge that was chosen in the functional connectome derived from a single fMRI run (REST1) shared the strongest correlation strength with the NIH Toolbox and CBCL-externalizing.The standard method corresponded to the brain-behavior associations derived from the full fMRI timeseries of the low-motion youth with a mean FD < 0.20 mm.The motion-ordered method corresponded to the brain-behavior associations derived from the scrubbed fMRI timeseries ranked and thresholded by their 100 least motion-corrupted timepoints (0 < FD < 0.20 mm) to construct the functional connectivity matrices of the low-motion youth.The sample sizes were bootstrapped at 11 logarithmically-spaced , 41, 66, 106, 172, 279, 453, 733, 1188, 1925, 3120};Black N ∈ {25, 34, 47, 65, 89, 122, 168, 230, 316, 434, 596};Hispanic N ∈ {25, 36, 52, 75, 109, 157, 227, 328, 474, 685, 990}.Solid teal and purple lines show the mean correlations from the 500 bootstrap samples for a given same size.Teal and purple shadings denote the minimum and maximum correlations across 500 bootstrap samples for a given sample size.Black dotted lines represent the lower and upper bounds of the 95% CIs for a given sample size.The areas under the curve (AUC) for the brain-behavior associations also are displayed.
The effect sizes produced by the standard and motion-ordered methods from REST1 remained comparable for the NIH Toolbox (1.00% < AUC < 3.91%) and CBCL-externalizing (1.34% < AUC < ∆ ∆ 2.18%) across the 3 racial/ethnic groups when the high-motion youth were included.

Supplementary Figure 7. Correlations between functional connectivity and (A-B) NIH Toolbox and (C-D)
CBCL-externalizing using the standard and motion-ordered methods as a function of sample size across the 3 low-/high-motion racial/ethnic groups obtained from REST1.The respective edge that was chosen in the functional connectome derived from a single fMRI run (REST1) shared the strongest correlation strength with the NIH Toolbox and CBCL-externalizing.The standard method corresponded to the brain-behavior associations derived from the full fMRI timeseries of the low-/high-motion youth that have been retained for the analyses without imposing an initial head motion threshold of mean FD < 0.20 mm.The motion-ordered method corresponded to the brain-behavior associations derived from the scrubbed fMRI timeseries of the low-/high-motion youth who were retained based on the assumption that they had a minimum of 100 least motion-corrupted timepoints.Their scrubbed fMRI timeseries were ranked by their lowest FD values and 100 least motion-corrupted timepoints (0 < FD < 0.20 mm) were selected to construct the functional connectivity matrices of the youth.The sample sizes were bootstrapped at 11 logarithmically-spaced N intervals: White N ∈ {25, 41, 67, 111, 182, 299, 491, 806, 1324, 2174, 3571};Black N ∈ {25, 35, 50, 70, 98, 138, 194, 274, 385, 542, 763};Hispanic N ∈ {25, 37, 54, 80, 117, 173, 254, 374, 550, 810, 1192}.Solid teal and purple lines show the mean correlations from the 500 bootstrap samples for a given same size.Teal and purple shadings denote the minimum and maximum correlations across 500 bootstrap samples for a given sample size.Black dotted lines represent the lower and upper bounds of the 95% CIs for a given sample size.The areas under the curve (AUC) for the brain-behavior associations also are displayed.

Supplementary Figure 8. Correlations between functional connectivity and (A-B) NIH Toolbox and (C-D)
CBCL-externalizing using the standard and bagging methods as a function of sample size across the 3 low-motion racial/ethnic groups obtained from REST1.The respective edge that was chosen in the functional connectome derived from a single fMRI run (REST1) shared the strongest correlation strength with the NIH Toolbox and CBCL-externalizing.The standard method corresponded to the brain-behavior associations derived from the full fMRI timeseries of the low-motion youth with a mean FD < 0.20 mm.The bagging method corresponded to the brain-behavior associations derived from the scrubbed fMRI timeseries ranked and thresholded by their 100 least motion-corrupted timepoints (0 < FD < 0.20 mm) from which 100 timepoints were bootstrapped across 500 iterations to construct the functional connectivity matrices of the low-motion youth.The sample sizes were bootstrapped at 11 logarithmically-spaced N intervals: White N ∈ {25, 41, 66, 106, 172, 279, 453, 733, 1188, 1925, 3120};Black N ∈ {25, 34, 47, 65, 89, 122, 168, 230, 316, 434, 596};Hispanic N ∈ {25, 36, 52, 75, 109, 157, 227, 328, 474, 685, 990}.Solid teal and purple lines show the mean correlations from the 500 bootstrap samples for a given same size.Teal and purple shadings denote the minimum and maximum correlations across 500 bootstrap samples for a given sample size.Black dotted lines represent the lower and upper bounds of the 95% CIs for a given sample size.The areas under the curve (AUC) for the brain-behavior associations also are displayed.
The effect sizes produced by the standard and bagging methods from REST1 remained comparable for the NIH Toolbox (0.58% < AUC < 4.90%) and CBCL-externalizing (0.37% < AUC < 0.90%) ∆ ∆ across the 3 racial/ethnic groups when the high-motion youth were included.

Supplementary Figure 9. Correlations between functional connectivity and (A-B) NIH Toolbox and (C-D)
CBCL-externalizing using the standard and bagging methods as a function of sample size across the 3 low-/high-motion racial/ethnic groups obtained from REST1.The respective edge that was chosen in the functional connectome derived from a single fMRI run (REST1) shared the strongest correlation strength with the NIH Toolbox and CBCL-externalizing.The standard method corresponded to the brain-behavior associations derived from the full fMRI timeseries of the low-/high-motion youth that have been retained for the analyses without imposing an initial head motion threshold of mean FD < 0.20 mm.The bagging method corresponded to the brain-behavior associations derived from the scrubbed fMRI timeseries of the low-/high-motion youth who were retained based on the assumption that they had a minimum of 100 least motion-corrupted timepoints.Their scrubbed fMRI timeseries were ranked by their lowest FD values and 100 least motion-corrupted timepoints (0 < FD < 0.20 mm) were selected from which 100 timepoints were bootstrapped across 500 iterations to construct the functional connectivity matrices of the youth.The sample sizes were bootstrapped at 11 logarithmically-spaced N intervals: White N ∈ {25, 41, 67, 111, 182, 299, 491, 806, 1324, 2174, 3571};Black N ∈ {25, 35, 50, 70, 98, 138, 194, 274, 385, 542, 763};Hispanic N ∈ {25, 37, 54, 80, 117, 173, 254, 374, 550, 810, 1192}.Solid teal and purple lines show the mean correlations from the 500 bootstrap samples for a given same size.Teal and purple shadings denote the minimum and maximum correlations across 500 bootstrap samples for a given sample size.Black dotted lines represent the lower and upper bounds of the 95% CIs for a given sample size.The areas under the curve (AUC) for the brain-behavior associations also are displayed.
method corresponded to the brain-behavior associations derived from the full fMRI timeseries of the low-/high-motion youth that have been retained for the analyses without imposing an initial head motion threshold of mean FD < 0.20 mm.The motion-ordered method corresponded to the brain-behavior associations derived from the scrubbed fMRI timeseries of the low-/high-motion youth who were retained based on the assumption that they had a minimum of 100 least motion-corrupted timepoints.Their scrubbed fMRI timeseries were ranked by their lowest FD values and 100 least motion-corrupted timepoints (0 < FD < 0.20 mm) were selected to construct the functional connectivity matrices of the youth.The sample sizes were bootstrapped at 11 logarithmically-spaced N intervals: White N ∈ {25, 41, 68, 112, 184, 303, 499, 822, 1355, 2231, 3675};Black N ∈ {25, 35, 50, 71, 100, 142, 201, 285, 404, 572, 810};Hispanic N ∈ {25, 37, 55, 81, 119, 177, 261, 386, 571, 843, 1247}.Solid teal and purple lines show the mean correlations from the 500 bootstrap samples for a given same size.Teal and purple shadings denote the minimum and maximum correlations across 500 bootstrap samples for a given sample size.Black dotted lines represent the lower and upper bounds of the 95% CIs for a given sample size.The areas under the curve (AUC) for the brain-behavior associations also are displayed.
method corresponded to the brain-behavior associations derived from the full fMRI timeseries of the low-/high-motion youth that have been retained for the analyses without imposing an initial head motion threshold of mean FD < 0.20 mm.The bagging method corresponded to the brain-behavior associations derived from the scrubbed fMRI timeseries of the low-/high-motion youth who were retained based on the assumption that they had a minimum of 100 least motion-corrupted timepoints.Their scrubbed fMRI timeseries were ranked by their lowest FD values and 100 least motion-corrupted timepoints (0 < FD < 0.20 mm) were selected from which 100 timepoints were bootstrapped across 500 iterations to construct the functional connectivity matrices of the youth.The sample sizes were bootstrapped at 11 logarithmically-spaced N intervals: White N ∈ {25, 41, 68, 112, 184, 303, 499, 822, 1355, 2231, 3675};Black N ∈ {25, 35, 50, 71, 100, 142, 201, 285, 404, 572, 810};Hispanic N ∈ {25, 37, 55, 81, 119, 177, 261, 386, 571, 843, 1247}.Solid teal and purple lines show the mean correlations from the 500 bootstrap samples for a given same size.Teal and purple shadings denote the minimum and maximum correlations across 500 bootstrap samples for a given sample size.Black dotted lines represent the lower and upper bounds of the 95% CIs for a given sample size.The areas under the curve (AUC) for the brain-behavior associations also are displayed.

Table 1 . Demographic, behavioral, and fMRI characteristics derived from the ABCD Study NIMH Data Archive Release 4.0.
CBCL = ChildBehavior Checklist indexing externalizing and internalizing behaviors.e Frames = number of volumes acquired across 4 resting-state scans.f tSNR = temporal signal-to-noise ratio.g FD = Framewise Displacement.Note that the externalizing and internalizing CBCL and NIH Toolbox scores were -standardized.
a ADI = Area Deprivation Index.b Participant sex denoted youth's sex assigned at birth.c NIH Toolbox = National Institutes of Health Toolbox indexing cognitive performance.d